DNA-based arrays can provide a simple way to explore the expression of a single polymorphic gene or a large number of genes. When the expression of a single gene is explored, DNA-based arrays are employed to detect the expression of specific gene variants. For example, a p53 tumor suppressor gene array is used to determine whether individuals are carrying mutations that predispose them to cancer. The array has over 50,000 DNA probes to analyze more than 400 distinct mutations of p53. A cytochrome p450 gene array is useful to determine whether individuals have one of a number of specific mutations that could result in increased drug metabolism, drug resistance, or drug toxicity.
DNA-based array technology is especially relevant for the rapid screening of expression of a large number of genes. There is a growing awareness that gene expression is affected in a global fashion. A genetic predisposition, disease, or therapeutic treatment may affect, directly or indirectly, the expression of a large number of genes. In some cases the interactions may be expected, such as where the genes are part of the same signaling pathway. In other cases, such as when the genes participate in separate signaling pathways, the interactions may be totally unexpected. Therefore, DNA-based arrays can be used to investigate how genetic predisposition, disease, or therapeutic treatment affect the coregulation and expression of a large number of genes.
It would be advantageous to prepare DNA-based arrays that can be used for monitoring the expression of a large number of proteins associated with cell proliferation or receptors. Proteins associated with cell proliferation include cytokines, hormones, growth and differentiation factors, G and ras-related proteins, lectins, oncogenes and their suppressors, and the like. Receptors include G protein coupled, four transmerrmbrane, tyrosine kinase, and nuclear receptors. Some of these proteins may be secreted and typically include signal sequences that direct proteins to their cellular or extracellular destination.
The present invention provides for a composition comprising a plurality of polynucleotide probes for use in detecting changes in expression of a large number of genes which encode proteins associated with cell proliferation and receptors. Such a composition can be employed for the diagnosis and for monitoring the treatment of any disease--a cancer, an immunopathology, a neuropathology and the like--where a defect in the expression of a gene which encodes a protein associated with cell proliferation or a receptor is involved.